PROJECT SUMMARY Respiratory weakness is a common manifestation of many neuromuscular diseases, including amyotrophic lateral sclerosis (ALS), myasthenia gravis, Guillain-Barre syndrome, and certain muscular dystrophies. Standard pulmonary function tests (PFTs) suffer from a number of limitations. These include: 1. inability to obtain accurate data in patients with concomitant bulbar weakness 2. Reliance on the patient being able to cooperate effectively; 3. Inability to obtain continuous assessment, especially when the patient is in the intensive care unit; 4. It provides no insight into pulmonary condition, including the presence of atelectasis. One approach that offers a potential more effective means for monitoring pulmonary function is via the application of electrical impedance tomography (EIT). In EIT, a belt embedded with multiple surface electrodes is placed around the chest and a low-resolution image is obtained by passing a very weak, non-ionizing electrical current between varying sets of electrodes and measuring the resulting voltages. Real-time videos of breathing can be obtained with the patient at rest breathing comfortably and also with full inspiration and expiration. From these images, simple metrics of pulmonary function can be derived. The technology has already found use in critical care patients with a variety of disorders and is very safe, it is even being used in premature infants to help monitor pulmonary condition and lung maturation. In this R21 proposal, we seek to establish the specific application of this technology in patients at risk for or with pulmonary dysfunction with ALS since they represent a group in whom the technology may be especially useful. In specific aim 1, we plan to assess the reliability of the technique in both ALS patients and age- and sex-matched healthy controls and to determine its relative sensitivity to pulmonary dysfunction. In specific aim 2, we will determine the relationship between EIT values and standard pulmonary function parameters both cross-sectionally and longitudinally over an approximately 3-month period of time, in patients both with and without concomitant bulbar weakness. At the end of this study we hope to have demonstrated the potential value for EIT the assessment of pulmonary function in ALS, opening the door to its wide application in the acute and chronic care of patients across a range of neuromuscular diseases.